Despite newer breakthrough medicines, the burden of diabetes and comorbid conditions – including obesity, cardio-renal disease, and others – continues to rise at an alarming rate. This meeting will explore gaps and challenges pertaining to our understanding of pathobiology and emerging therapeutic approaches that hold promise for addressing unmet clinical needs and reversing the trajectory of disease progression. The conference aims to share knowledge, spark scientific collaboration, and generate new research and development ideas. It will focus on three themes: (1) basic science, including genetic research into disease causation; (2) novel therapeutic targets and strategies, emphasizing non-incretin and disease-modifying approaches; and (3) innovative research and clinical tools. A broad mix of scientists will gather to share data, insights, and forward-thinking concepts. The meeting will bring together established and early-career researchers from diverse fields who infrequently collaborate, creating a unique platform for interaction among academic researchers, industry scientists, and clinical investigators. As the first Keystone meeting of its kind focused on metabolic disease, this forum will span basic research, translational science, and clinical drug development. The ability to hear the latest from, and directly interact with, exceptional scientists in this field is assured. Other aspects of the program will include interactive and multi-disciplinary workshops focusing on lessons from clinical trials and on health disparities.